Marshall L. Fishman

Pectin-based systems for colon-specific drug delivery via oral route

Pectin-derived matrices are now being examined and tested for controlled drug delivery. Pectin is intact in the upper gastrointestinal tract and degraded by colonic microflora. The composition of this microflora remains relatively consistent across a diverse human population. Thus, pectin-derived drug carriers provide promising potential for colon-specific drug delivery. This paper reviews recent developments in pectin-derived formulations. Subjects reviewed include gelation of pectin, calcium cross-linked pectinate, composites of pectin and other polymers, technologies to fabricate pectin into useful drug delivery vehicles, and methods to evaluate release kinetics of incorporated drugs. This article discusses advantages, limitations, and possible future developments in pectin-based formulations with particular emphasis on the field of colon-specific drug delivery.

Extrusion of pectin/starch blends plasticized with glycerol

Abstract The microstructural and thermal dynamic mechanical properties of extruded pectin/starch/glycerol (PSG) edible and biodegradable films were measured by scanning electron microscopy (SEM) and thermal dynamic mechanical analysis (TDMA). SEM revealed that the temperature profile (TP) in the extruder and the amount of water present during extrusion could be used to control the degree to which the starch was gelatinized. TDMA revealed that moisture and TP during extrusion and by inference the amount of starch gelatinization had little effect on the mechanical properties of PSG films. Furthermore, TDMA revealed that PSG films underwent a glass transition commencing at about −50°C and two other thermal transitions above room temperature. Finally, it was concluded that the properties of extruded PSG films were comparable to those cast from solution.

Characterization of pectin, flash-extracted from orange albedo by microwave heating, under pressure.

Pectin was acid extracted from orange albedo by microwave heating under pressure. Extraction times ranged from 2.5 to 8 min. Solubilized pectin was characterized for molar mass (M), rms radius of gyration (Rg) and intrinsic viscosity [eta] by HPSEC with online light scattering and viscosity detection. M, Rg and [eta] all decreased with increasing extraction time. Nevertheless, at heating times of 2.5 and 3.0 min, M, Rg and [eta] were significantly higher than a commercial citrus pectin when the albedo:solvent ratio was 1:25 (w/v). At the heating time of 2.5 min Mw was 3.6 x 10(5), Rgz was 38 nm and [eta]w was 10.8 dL/g. Chromatography revealed that solubilized pectin distributions were bimodal in nature and that the low-molar-mass fraction increased at the expense of the high-molar-mass fraction with increasing extraction time. Scaling law exponents revealed that the high-molar-mass fraction was extremely compact in shape, whereas the low-molar-mass fraction was more asymmetric in shape. Possibly these results indicated that at short extraction times, pectin was solubilized as compact aggregated network structures that were broken down to their more asymmetric components with increased heating times.

An Improved Process for Isolation of Corn Fiber Gum

ABSTRACT Sequential alkaline extraction and alkaline hydrogen peroxide (AHP) bleaching have been used to prepare corn fiber gum in yields ranging from 21 to 40%, depending on the pH of the extraction medium. The pH was adjusted by using different ratios of NaOH and Ca(OH)2 The whitest product was obtained after AHP bleaching of the extract obtained using the lowest pH value. In order for the product gum to give its characteristic clear and low viscosity solutions, it was necessary to remove starch from the corn fiber substrate using α-amylase. The water-insoluble hemicellulose A fraction, a minor component, was removed by neutralizing AHP-treated extracts before ethanol precipitation of the useful hemicellulose B (corn fiber gum) fraction. At ambient temperature, AHP bleaching was near optimal after ≈2 hr under the processing conditions used. High ratios of arabinose (39%) to xylose (50%) were present in the corn fiber gum extracted under various alkaline conditions, and the H2O2 processing step did not s...

Global Structure of Microwave-Assisted Flash-Extracted Sugar Beet Pectin

The global structure of microwave-assisted flash-extracted pectins isolated from fresh sugar beet pulp has been studied. The objective was to minimize the disassembly and possibly the degradation of pectin molecules during extraction. These pectins have been characterized by high-performance size exclusion chromatography with light scattering, viscometric detection, and atomic force microscopy (AFM). Analysis of molecular parameters was performed on 15 and 8 microm size column packings. Samples analyzed with 15 microm packing gave weight-average molar masses that ranged from 532,000 to 1.2 million Da, radii of gyration from about 35 to 51 nm, polydispersities from 1.78 to 2.58, intrinsic viscosities from about 3.00 to 4.30 dL/g, and recoveries from 8.40 to 14.81% of dry weight. Chromatography revealed that a bimodal distribution of high molar mass spherical particles and lower molar mass coils was obtained. AFM images of pectin corroborated this conclusion and further revealed that these strands and spherical particles were integrated into networks. It is demonstrated that microwave-assisted extraction of sugar beet pulp under moderate pressure and at relatively low temperature could extract under acid conditions high molar mass, moderate-viscosity pectin in minutes rather than hours as required by conventional heating.

Pectin/Zein Beads for Potential Colon-Specific Drug Delivery: Synthesis and in Vitro Evaluation

Novel complex hydrogel beads were prepared from two edible polymers: pectin, a carbohydrate from citrus fruits, and zein, a protein from corn. The pectin/zein complex hydrogels did not swell in physiological environments, but hydrolyzed in the presence of pectinases. An in vitro study showed the capacity of the hydrogels to endure protease attack and residence time variation. The physical and biological properties of the new hydrogels were attributed to molecular entanglement of the two polymers. The pectin networks were stabilized by the bound zein molecules. In turn, the pectin networks shielded the bound zein from protease digestion.

Thermomechanical properties of blends of pectin and poly(vinyl alcohol)

Blends of citrus pectin and several types of poly(vinyl alcohol) were investigated to determine the effects of compositional variables and polymer type on film properties. Some films were also plasticized with glycerol. Films were cast from water onto Lexan™ plates, dried, and removed. Thermomechanical properties were obtained using a dynamic mechanical analyzer, and thermodynamic transitions were also obtained using a differential scanning calorimeter. Increasing the amount of poly(vinyl alcohol) in the blends reduced the storage and loss modulus of the films above the glass transition temperature (Tg). The Tg values observed decreased as the amount of PVOH in the blend increased. Addition of glycerol depressed the PVOH Tg and merged it into the Tg of the pectin/glycerol blend. Changes in the molecular weight and degree of ester hydrolysis of poly(vinyl alcohol) exerted a rather small effect on the blends.

Characterization of starches dissolved in water by microwave heating in a high pressure vessel

Starch granules derived from four corn varieties were dispersed in water and depending on variety about 49–71% of the granules dissolved by microwave heating in a high pressure vessel (MWHPV). The apparent ratios of amylopectin to amylose were 1:0, 3:1, 1:1 and 3:7. High performance size exclusion chromatography (HPSEC) was carried out using two μ Bondagel† and one Synchropak† HPSEC columns placed in series. These had size exclusion limits specified by their manufacturers as 400 nm, 100 nm, and 10 nm, respectively. The mobile phase was 0.05 m NaNO3. For each starch composition, refractive index and viscosity chromatograms were obtained and fitted with the same six Gaussian components by nonlinear regression analysis. Calibration of the column set with pullulan and dextran standards in hydrodynamic volume and root mean square radius of gyration (Rg) enabled calculation of the intrinsic viscosity (IV), molecular weight (M), and Rg for each component in addition to global values of these quantities for the entire distribution. Analysis of the data revealed that as starches eluted from the column set, there were large changes in M and Rg and rather small changes in IV. Furthermore, MWHPV containing water as employed here produces starch of relatively large molecular weight and size but low intrinsic viscosity leading to the conclusion that dense starch granule fragments were solubilized.

Identification of extensin protein associated with sugar beet pectin.

Several studies have suggested that the emulsification properties associated with pectin obtained from sugar beet (Beta vulgaris) are due to the presence of a protein-pectin complex. Nevertheless, the identity of the protein has remained elusive. Pectin, extracted from sugar beet pulp by microwave-assisted extraction, and a commercial sample were both subjected to protease digestion with trypsin. The resulting peptides were separated from the pectin solution by ultrafiltration using a 3 kDa molecular weight cutoff (MWCO) membrane and analyzed using matrix-assisted laser desorption ionization with tandem time-of-flight mass spectrometry. The partial sequences derived from the mass spectrometry analyses of the resulting tryptic peptides are found to be highly consistent with extensin protein matched from the B. vulgaris Genetic Index database and also correspond to previously reported extensin peptides found in sugar beet cell suspension cultures. Further attempts were made to disassociate the protein from pectin using 1 M NaCl and a 100 kDa MWCO membrane; however, no peptides were observed following trypsin digestion of the permeate solution. This evidence suggests the existence of a complex between the pectin and extensin that is not due to ionic interactions. Trypsin digestion of commercial sugar beet pectin also produced the peptide profile observed with the microwave-assisted extracted pectin sample. Atomic force microscopy established that the number of rod-like elements decreased following protease treatment compared to the untreated sample.

Macromolecular characterisation of three barley β-glucan standards by size-exclusion chromatography combined with light scattering and viscometry: an inter-laboratory study

Abstract Six (1→3)(1→4)-β- d -glucan standards (A–F) isolated from barley were analysed by size-exclusion chromatography (SEC) in five different laboratories with varying columns, solvent conditions and detector systems (low- and multi-angle light scattering and viscometry). Static (batch) measurements by capillary viscometry and laser light scattering were included. Fairly consistent results were obtained for the weight average molecular weights (Mw), radii of gyration (RG) and intrinsic viscosities [η], demonstrating that the β-glucans may serve as useful standards or reference materials in the study of cereal β-glucans. Average values for Mw were: A,E: 114,000 (±11%); B,C: 374,000 (±9%), D,F: 228,000 (±13%). Some inconsistencies regarding the polydispersity (Mw/Mn) could be ascribed to the influence of peak broadening in certain column/solvent systems. The study further demonstrated that individual researchers tended to use different processing parameters, especially refractive index increments (dn/dc), due to ambiguities in the literature or to differing experimental values. The need for consistent parameters and processing methods is clearly demonstrated.